1. Field of the Invention
This invention relates to a process for the production of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penams. More particularly, it relates to a chemical process for the conversion of 6-acylamido-2,2-dimethyl-3-(5-tetrazolyl)penams, and especially of 6-(2-phenylacetamido)- and 6-(2-phenoxyacetamido)-2,2-dimethyl-3-(5-tetrazolyl)penams and certain derivatives thereof which carry a blocking or pseudo blocking group on the tetrazolyl moiety, to 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penams.
2. Description of the Prior Art
6-AMINO-2,2-DIMETHYL-3-(5-TETRAZOLYL)PENAM (FORMULA I below and certain derivatives thereof wherein a blocking or pseudo blocking group is attached to the 1- or 2- position of the tetrazolyl moiety are valuable intermediates for the sythesis of a new class of antibacterial agents; namely, 6-acylamido-2,2-dimethyl-3-(5-tetrazolyl)penams. Such compounds are described in U.S. application Ser. Nos. 407,097, 450,435, and 491,510 filed Oct. 17, 1973, Mar. 12, 1974 and July 24, 1974 respectively, each of said applications now being abaondoned.
The chemical cleavage of acyl side chains from penicillins and cephalosporins is described in U.S. Pat. No. 3,499,909. The process comprises protection of the carboxyl groups of the penicillins or cephalosporins by converting them to silyl esters. The silyl esters are then reacted with a halogenating agent below about 0.degree. C. to produce an imino chloride which is then treated with an alcohol below about -20.degree. C. The imino ether thus produced is then hydrolyzed under acid conditions to provide 6-aminopenicillanic acid or 7-aminocephalosporanic acid.
For the sake of convenience, the compounds described herein are identified as derivatives of penam. The term "penam" has been defined by Sheehan et al. in the Journal of the American Chemical Society, 75 3293 (1953), as referring to the structure ##SPC1##
Using this terminology, the well-known antibiotic penicillin G is designated as 6-(2-phenylacetamido)-2,2-dimethyl-penam-3-carboxylic acid.
Many of the reactants of this invention are also 5-substituted tetrazoles, and 5-substituted tetrazoles can exist in two isomeric forms, viz: ##STR1## As will be appreciated by one skilled in the art, when the substituent represented by R.sub.1 or R.sub.2 is hydrogen, the two forms co-exist in a dynamic tautomeric, equilibrium mixture. However, in the case where R.sub.1 or R.sub.2 represent a substituent other than hydrogen, the two forms represent different chemical entities which do not spontaneously interconvert.